Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers and insulates the nerves and nerve fibers. Myelin damage disrupts communication between the brain’s neurons and between the brain and body and can damage the axons of the nerve cells. The damaged myelin forms scar tissue (sclerosis), causing nerve impulses traveling to and from the brain and spinal cord to become distorted or interrupted, which can lead to symptoms ranging from numbness and tingling to weakness, vertigo, pain, and speech, gait, and vision problems. Disease activity continues even when there are no symptoms. The process can continue to deteriorate the cells irreversibly.

MS affects more than 400,000 people in the United States—about 25,000 of them children. Most people are diagnosed between the ages of 20 and 40, and the disease occurs about three times more often in women than in men.

Multiple Factors
The cause of multiple sclerosis is unknown. A combination of factors, ranging from genetic susceptibility to inflammation and environmental influences, may play a role. MS is more common in areas farthest from the equator; although ethnicity appears to be a factor and the age when a person migrates north or south also appears to influence its occurrence. Scientists believe that environmental factors, such as vitamin D or sunlight, may also play a part.

Genetic and genomic studies are helping to identify genes that affect a person’s susceptibility to developing the disease. Research has shown that a group of genes called the major histocompatibility complex (MHC) controls the immune response through cell surface proteins which bind antigens that let the immune system’s T cells recognize it as “self” or “foreign.” MS is considered an autoimmune disease because the immune system mistakenly attacks its own tissue.

Its more common symptoms include double vision or other vision problems, numbness or tingling in the arms and legs, tremor or lack of coordination, dizziness, overall weakness, vertigo, and numbness starting in the lower body and moving upwards. There is no single test for MS, and other conditions, such as Lyme disease and B-12 deficiency, can mimic its symptoms.

Careful Diagnosis
A clinical diagnosis is determined using well-established McDonald criteria through a careful medical history of episodes of attacks, neurologic exam, and supporting evidence from magnetic resonance imaging (MRI), lumbar puncture, and blood tests to exclude other conditions. Visual evoked potentials and/or other assessment tools are also sometimes used.

A lumbar puncture or spinal tap will show if there are oligoclonal bands, proteins called immunoglobulins that indicate inflammation of the central nervous system. These bands are present in 90 percent of MS cases. MRI can reveal brain lesions associated with MS, even when there are no symptoms. These imaging tests involve the use of gadolinium, a contrast agent that accumulates in active plaques. Lesions occur in the periventricular and juxtacortical areas and posterior fossa, which contain the parts of the brain involved in coordination and motor function, as well as in the spinal cord.

MS appears to include more than one disease and may include a spectrum of syndromes. For example, neuromyelitis optica (NMO) is an autoimmune disease with similar symptoms in which immune system cells primarily attack the optic nerves and the spinal cord. It is thought to be caused by B cells and is treated differently than MS, usually with plasma exchange (PLEX) and B-cell depleting treatments, to lower the levels of anti-aquaporin 4 antibody in the blood.

“MS is not just one condition,” Dr. Lock said. “In one proposed classification system, MS has been divided into four distinct types, with different pathologies.”

Treatment Options
There is no cure for MS, but there are treatments to slow the course of the disease, manage symptoms, reduce inflammation, and modify relapses.

“It’s important to start treatment early to protect the brain,” said Dr. Lock. “Neurons may be lost and atrophy may occur if MS is untreated, and the loss can be rapid.”

Several medications that regulate the immune system have been in use for years, including the so-called ABC drugs: Avonex (interferon beta-1a) and Betaseron (interferon beta-1b), which are types of beta interferons; and Copaxone (glatiramer acetate), which modifies the T-cell response to myelin. New drugs are in development, and there currently are 13 FDA-approved medications to treat MS. Several new drugs, such as Tysabri (natalizumab), Lemtrada (alemtuzumab), and fumarate, are monoclonal antibodies that recognize and bind to specific cell receptors and antigens to override an immune cell response.

Patients generally are treated first with an injectable or oral drug, Dr. Lock said. Relapses are usually treated with corticosteroids. The overall goal is to gain complete control of the inflammation to allow the neurons to repair and regenerate, what neurologists refer to as NEDA—no evidence of disease activity.

A number of clinical trials are under way to test new drugs and targets. More attention is being paid to B cells, and a promising new monoclonal antibody called ocrelizumab is under development that targets B cells. Because myelin has the capacity to repair, which drops over time, other studies are looking at drugs to promote myelin regrowth. One of the most promising new directions is in using blood samples to identify biomarkers that can then be used to individualize treatment; biomarkers may show how a person will respond to medication or predict who may be at risk.

“There are more drugs available now, and more in the pipeline,” Dr. Lock said. “It’s a very hopeful time.”

About the Speaker
Christopher Lock, PhD, a clinical associate professor of neurology and neurological sciences, is a specialist in multiple sclerosis and neuroimmunology. Before coming to Stanford in May 2015, he worked at Carantech Biosciences Inc., a biotechnology startup, and was a neurologist at the Palo Alto Medical Foundation. He received his medical degree from Westminster Hospital Medical School, University of London, and did an internship, residency, and fellowship at Stanford. He is Board Certified by the American Board of Psychiatry and Neurology and is a member of the American Academy of Neurology, the San Francisco Neurological Society, and the California Neurology Society.